Effect of irisin on the epilepsy induced by penicillin G: An electrophysiological study

Year 2022, Volume: 39 Issue: 4, 1061 - 1067, 29.10.2022

Yasemin Şahin Yıldız , Şerif Demir , Ersin Beyazçiçek , Ali Gök , Özge Beyazçiçek

Abstract

Epilepsy is a neurological disease characterized by sudden and synchronized seizures caused by abnormal and excessive electrical discharges in brain neurons. The purpose of this study was to electrophysiologically examine the effects of acute administration of irisin, which is thought to be neuroprotective and increase cell proliferation, at different doses (10 and 100 nM) on the penicillin-induced experimental epilepsy in rats. Forty-nine adult male Wistar rats were used in the study. The rats were divided into 7 groups: sham, control group (penicillin), irisin group, the pre- and during-seizure groups of 10 nM and 100 nM irisin. All the substances except penicillin were administered intraperitoneally. The rats were anesthetized using urethane. The bone tissue on the left cerebral cortex was removed and the electrodes were placed in the somatomotor cortex. Thirty minutes before penicillin administration, irisin was administered to the pre-seizure penicillin group at doses of 10 nM and 100 nM. Then, penicillin (500 IU/2 µl) was injected intracortically, and ECoG recording was continued for 120 minutes. On the other hand, 10 nM and 100 nM of irisin were administered to the during-seizure penicillin group after penicillin was injected intracortically and the seizure occurred, and ECoG recording was continued for 120 minutes. The ECoG recordings were analyzed using the PowerLab Chart v.8 software. In conclusion, it was found that irisin prolonged the latency of initial epileptic activity and decreased the number and amplitude of spike-waves in the penicillin-induced experimental epilepsy model. These results suggest that irisin might have an antiepileptic potential.

Keywords

Electrocorticography, Epilepsy, Epileptiform Activity, İrisin, Rat

Supporting Institution

Düzce University

Project Number

2020.04.01.1074.

Thanks

This study was financed by the Düzce University Research Foundation (BAP-grand number:2020.04.01.1074). This study was written from thesis no.690262, whose information is given below. Effect of Irisin on The Epilepsy Induced by Penicillin G. Author: Yasemin Şahin Yıldız Supervisor: Prof.Dr. Şerif Demir. Department of Physiology, Medical School, University of Düzce, Düzce, Turkey

References

• 1. Aygun H. Exendin-4 increases absence-like seizures and anxiety–depression-like behaviors in WAG/Rij rats. Epilepsy Behav [Internet]. 2021 Oct [cited 2022 Feb 11];123:108246. Available from: https://doi.org/10.1016/j.yebeh.2021.108246
• 2. Sarlo GL, Holton KF. Brain concentrations of glutamate and GABA in human epilepsy: A review. Seizure. 2021 Oct 1;91:213–27.
• 3. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475–82.
• 4. Newton CR, Garcia HH. Epilepsy in poor regions of the world. Lancet [Internet]. 2012 [cited 2022 Feb 16];380:1193–201. Available from: www.thelancet.com
• 5. Espinosa-Jovel C, Toledano R, Aledo-Serrano Á, García-Morales I, Gil-Nagel A. Epidemiological profile of epilepsy in low income populations. Seizure Eur J Epilepsy [Internet]. 2018 [cited 2020 Jul 16];56:67–72. Available from: https://doi.org/10.1016/j.seizure.2018.02.002
• 6. do Canto AM, Donatti A, Geraldis JC, Godoi AB, da Rosa DC, Lopes-Cendes I. Neuroproteomics in Epilepsy: What Do We Know so Far? Front Mol Neurosci [Internet]. 2021 Jan 7 [cited 2022 Feb 21];13:254. Available from: https://www.frontiersin.org/articles/10.3389/fnmol.2020.604158/full
• 7. Lee-Lane E, Torabi F, Lacey A, Fonferko-Shadrach B, Harris D, Akbari A, et al. Epilepsy, antiepileptic drugs, and the risk of major cardiovascular events. Epilepsia [Internet]. 2021 Jul 1 [cited 2022 Feb 22];62(7):1604–16. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/epi.16930
• 8. Kobayashi K, Endoh F, Ohmori I, Akiyama T. Action of antiepileptic drugs on neurons. Brain Dev [Internet]. 2020;42(1):2–5. Available from: https://doi.org/10.1016/j.braindev.2019.07.006
• 9. Govil N, Chahal S, Gupta N, Kaloti AS, Nadda A, Singh P. Factors Associated with Poor Antiepileptic Drugs Adherence in below Poverty Line Persons with Epilepsy: A Cross-Sectional Study. J Neurosci Rural Pract [Internet]. 2021 Jan 1 [cited 2022 Feb 22];12(1):95–101. Available from: http://www.thieme-connect.de/products/ejournals/html/10.1055/s-0040-1721200
• 10. Taşkiran E, Bebek N. Drug Resistance and Resistance Mechanisms in Epilepsy. J Turkish Epilepsi Soc. 2015;21(2):43–53.
• 11. Erdoğan MA, Erbaş O. Anticonvulsant Effect of Oxolamine Citrate in Pentylenetetrazole Induced Experimental Epilepsy Model in Rats. Suleyman Demirel Univ J Heal Sci. 2020;11(1):92–9.
• 12. Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1a dependent myokine that derives browning of white fat and thermogenesis. Nature. 2012;481(7382):463–8.
• 13. Leustean L, Preda C, Teodoriu L, Mihalache L, Arhire L, Ungureanu MC. Role of Irisin in Endocrine and Metabolic Disorders—Possible New Therapeutic Agent? Appl Sci 2021, Vol 11, Page 5579 [Internet]. 2021 Jun 16 [cited 2022 Mar 2];11(12):5579. Available from: https://www.mdpi.com/2076-3417/11/12/5579/htm
• 14. Pignataro P, Dicarlo M, Zerlotin R, Zecca C, Dell’abate MT, Buccoliero C, et al. Fndc5/irisin system in neuroinflammation and neurodegenerative diseases: Update and novel perspective [Internet]. Vol. 22, International Journal of Molecular Sciences. MDPI AG; 2021 [cited 2021 May 5]. p. 1–14. Available from: /pmc/articles/PMC7915567/
• 15. Wu H, Guo P, Jin Z, Li X, Yang X, Tang C, et al. Serum levels of irisin predict short-term outcomes in ischemic stroke. Cytokine [Internet]. 2019 Oct 1 [cited 2021 Apr 29];122:2–6. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1043466618300577
• 16. Tu T, Yin S, Pang J, Zhang X, Zhang L, Zhang Y, et al. Irisin Contributes to Neuroprotection by Promoting Mitochondrial Biogenesis After Experimental Subarachnoid Hemorrhage. Front Aging Neurosci [Internet]. 2021 Feb 3 [cited 2021 Apr 29];13:1–15. Available from: https://www.frontiersin.org/articles/10.3389/fnagi.2021.640215/full
• 17. Lourenco M V., Frozza RL, de Freitas GB, Zhang H, Kincheski GC, Ribeiro FC, et al. Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models. Nat Med [Internet]. 2019 Jan 1 [cited 2021 Apr 29];25(1):165–75. Available from: https://pubmed.ncbi.nlm.nih.gov/30617325/
• 18. Asadi Y, Gorjipour F, Behrouzifar S, Vakili A. Irisin Peptide Protects Brain Against Ischemic Injury Through Reducing Apoptosis and Enhancing BDNF in a Rodent Model of Stroke. Neurochem Res [Internet]. 2018 Aug 1 [cited 2021 Apr 29];43(8):1549–60. Available from: https://doi.org/10.1007/s11064-018-2569-9
• 19. Tu WJ, Qiu HC, Cao JL, Liu Q, Zeng XW, Zhao JZ. Decreased Concentration of Irisin Is Associated with Poor Functional Outcome in Ischemic Stroke. Neurotherapeutics [Internet]. 2018 Oct 14 [cited 2021 Apr 29];15(4):1158–67. Available from: https://pubmed.ncbi.nlm.nih.gov/30030698/
• 20. Li DJ, Li YH, Yuan H Bin, Qu LF, Wang P. The novel exercise-induced hormone irisin protects against neuronal injury via activation of the Akt and ERK1/2 signaling pathways and contributes to the neuroprotection of physical exercise in cerebral ischemia. Metabolism [Internet]. 2017 Mar 1 [cited 2021 Apr 29];68:31–42. Available from: https://pubmed.ncbi.nlm.nih.gov/28183451/
• 21. Zarbakhsh S, Safari M, Aldaghi MR, Sameni HR, Lagmouj YK, Jaberi KR, et al. Irisin protects the substantia nigra dopaminergic neurons in the rat model of Parkinson ’ s disease. Iran J Basic Med Sci. 2019;22(7):722–8.
• 22. Kim OY, Song J. The Role of Irisin in Alzheimer’s Disease. J Clin Med. 2018;7(11):407.
• 23. Guo P, Jin Z, Wu H, Li X, Ke J, Zhang Z, et al. Effects of irisin on the dysfunction of blood-brain barrier in rats after focal cerebral ischemia/reperfusion. Brain Behav. 2019;9(10):1–9.
• 24. Elhady M, Youness ER, Gafar HS, Abdel Aziz A, Mostafa RSI. Circulating irisin and chemerin levels as predictors of seizure control in children with idiopathic epilepsy. Neurol Sci. 2018;39(8):1453–8.
• 25. Yıldırım M, Değirmenci U, Yalın S. The role of inflammation in epilepsy. Mersin Univ J Heal Sci. 2019;12(3):525–33.
• 26. Xiong XQ, Geng Z, Zhou B, Zhang F, Han Y, Zhou YB, et al. FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in obesity. Metabolism. 2018 Jun 1;83:31–41.
• 27. Myint PK, Ito A, Appiah MG, Obeng G, Darkwah S, Kawamoto E, et al. Irisin supports integrin-mediated cell adhesion of lymphocytes. Biochem Biophys Reports. 2021 Jul 1;26:100977.
• 28. Buscemi S, Corleo D, Vasto S, Buscemi C, Barile AM, Rosafio G, et al. Serum Irisin Concentrations in Severely Inflamed Patients. Horm Metab Res. 2020;52(4):246–50.
• 29. Mazur-Bialy AI. Irisin acts as a regulator of macrophages host defense. Life Sci. 2017 May 1;176:21–5.
• 30. Anand Narayanan S, Metzger CE, Bloomfield SA, Zawieja DC. Inflammation-induced lymphatic architecture and bone turnover changes are ameliorated by irisin treatment in chronic inflammatory bowel disease. FASEB J. 2018;32(9):4848–61.
• 31. Ergul Erkec O, Algul S, Kara M. Evaluation of ghrelin, nesfatin-1 and irisin levels of serum and brain after acute or chronic pentylenetetrazole administrations in rats using sodium valproate. Neurol Res [Internet]. 2018;40(11):923–9. Available from: https://doi.org/10.1080/01616412.2018.1503992
• 32. Gruhn K, Siteneski A, Camargo A, Freitas AE, Olescowicz G, Brocardo PS, et al. Physical exercise stimulates hippocampal mTORC1 and FNDC5/irisin signaling pathway in mice: Possible implication for its antidepressant effect. Behav Brain Res. 2021 Feb 26;400:1–8.
• 33. Huh JY, Siopi A, Mougios V, Park KH, Mantzoros CS. Irisin in Response to Exercise in Humans With and Without Metabolic Syndrome. J Clin Endocrinol Metab [Internet]. 2015 Mar 1 [cited 2021 May 5];100(3):453–7. Available from: https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2014-2416
• 34. Palacios-González B, Vadillo-Ortega F, Polo-Oteyza E, Sánchez T, Ancira-Moreno M, Romero-Hidalgo S, et al. Irisin levels before and after physical activity among school-age children with different BMI: A direct relation with leptin. Obesity. 2015;23(4):729–32.
• 35. Huh JY, Mougios V, Kabasakalis A, Fatouros I, Siopi A, Douroudos II, et al. Exercise-Induced Irisin Secretion Is Independent of Age or Fitness Level and Increased Irisin May Directly Modulate Muscle Metabolism Through AMPK Activation. J Clin Endocrinol Metab [Internet]. 2014 Nov 1 [cited 2021 May 5];99(11):2154–61. Available from: https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2014-1437
• 36. Jedrychowski MP, Wrann CD, Paulo JA, Gerber KK, Szpyt J, Robinson MM, et al. Detection and quantitation of circulating human irisin by tandem mass spectrometry. Cell Metab [Internet]. 2015 Oct 6 [cited 2021 May 5];22(4):734–40. Available from: /pmc/articles/PMC4802359/
• 37. Dehghan F, Zamani S, Barreiro C, Jami MS. Irisin injection mimics exercise effects on the brain proteome. Eur J Neurosci [Internet]. 2021 Nov 1 [cited 2022 Mar 7];54(10):7422–41. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/ejn.15493
• 38. de Lima C, Arida RM, Andersen ML, Polesel DN, de Alvarenga TAF, Vancini RL, et al. Effects of acute physical exercise in the light phase of sleep in rats with temporal lobe epilepsy. Epilepsy Res. 2017 Oct 1;136:54–61.
• 39. Folbergrová J, Kunz WS. Mitochondrial dysfunction in epilepsy. Mitochondrion [Internet]. 2012 Jan [cited 2022 Mar 6];12(1):35–40. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1567724911001851
• 40. Wu Y, Chen M, Jiang J. Mitochondrial dysfunction in neurodegenerative diseases and drug targets via apoptotic signaling. Mitochondrion. 2019 Nov 1;49:35–45.
• 41. Zhang J, Bi J, Ren Y, Du Z, Li T, Wang T, et al. Involvement of GPX4 in irisin’s protection against ischemia reperfusion-induced acute kidney injury. J Cell Physiol [Internet]. 2021 Feb 1 [cited 2022 Mar 6];236(2):931–45. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.29903
• 42. Bi J, Zhang J, Ren Y, Du Z, Li T, Wang T, et al. Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor. J Cell Mol Med. 2020 Jan 1;24(1):996–1009.
• 43. Cheng Y, Cui Y, Zhai Y, Xin W, Yu Y, Liang J, et al. Neuroprotective Effects of Exogenous Irisin in Kainic Acid-Induced Status Epilepticus. Front Cell Neurosci. 2021;15:738533.
• 44. Momenzadeh S, Zamani S, Dehghan F, Barreiro C, Jami MS. Comparative proteome analyses highlight several exercise-like responses of mouse sciatic nerve after IP injection of irisin. Eur J Neurosci. 2021 May 1;53(10):3263–78.
• 45. Sepehr A, Taheri F, Heidarian S, Motaghinejad M, Safari S. Neuroprotective and neuro-survival properties of safinamide against methamphetamine-induced neurodegeneration: Hypothetic possible role of BDNF/TrkB/PGC-1α signaling pathway and mitochondrial uncoupling protein −2(UCP-2). Med Hypotheses. 2020 Oct 1;143:110094.
• 46. Rabiee F, Lachinani L, Ghaedi S, Nasr-Esfahani MH, Megraw TL, Ghaedi K. New insights into the cellular activities of Fndc5/Irisin and its signaling pathways. Cell Biosci [Internet]. 2020;10(1):1–10. Available from: https://doi.org/10.1186/s13578-020-00413-3
• 47. Dey A, Kang X, Qiu J, Du Y, Jiang J. Anti-inflammatory small molecules to treat seizures and epilepsy: from bench to bedside. Trends Pharmacol Sci [Internet]. 2016 Jun 1 [cited 2022 Mar 11];37(6):463. Available from: /pmc/articles/PMC5064857/
• 48. Zhao YT, Wang H, Zhang S, Du J, Zhuang S, Zhao TC. Irisin Ameliorates Hypoxia/Reoxygenation-Induced Injury through Modulation of Histone Deacetylase 4. Fan G-C, editor. PLoS One [Internet]. 2016 Nov 22 [cited 2021 May 4];11(11):e0166182. Available from: https://dx.plos.org/10.1371/journal.pone.0166182
• 49. Mazur-Bialy AI, Pocheć E, Zarawski M. Anti-inflammatory properties of irisin, mediator of physical activity, are connected with TLR4/Myd88 signaling pathway activation. Int J Mol Sci [Internet]. 2017 Apr 1 [cited 2021 May 4];18(4). Available from: /pmc/articles/PMC5412287/
• 50. Rana A, Musto AE. The role of inflammation in the development of epilepsy. J Neuroinflammation 2018 151 [Internet]. 2018 May 15 [cited 2022 Mar 11];15(1):1–12. Available from: https://link.springer.com/articles/10.1186/s12974-018-1192-7
• 51. Ergul Erkec O, Milanlıoğlu A, Komuroglu AU, Kara M, Huyut Z, Keskin S. Evaluation of serum ghrelin, nesfatin-1, irisin, and vasoactive intestinal peptide levels in temporal lobe epilepsy patients with and without drug resistance: a cross-sectional study. Rev Assoc Med Bras [Internet]. 2021 [cited 2022 Feb 14];67(2):207–12. Available from: https://doi.org/10.1590/1806-9282.67.02.20200521
• 52. Bráz JM, Sharif-Naeini R, Vogt D, Kriegstein A, Alvarez-Buylla A, Rubenstein JL, et al. Forebrain GABAergic Neuron Precursors Integrate into Adult Spinal Cord and Reduce Injury-Induced Neuropathic Pain. Neuron [Internet]. 2012 May 24 [cited 2021 May 10];74(4):663–75. Available from: /pmc/articles/PMC3361692/
• 53. Li C, Lei Y, Tian Y, Xu S, Shen X, Wu H, et al. The etiological contribution of GABAergic plasticity to the pathogenesis of neuropathic pain. Mol Pain [Internet]. 2019 May 1 [cited 2021 May 10];15:1–13. Available from: /pmc/articles/PMC6509976/
• 54. Dun SL, Lyu R-M, Chen Y-H, Chang J-K, Luo JJ, Dun NJ. Irisin-immunoreactivity in neural and non-neural cells of the rodent. Neuroscience [Internet]. 2013 Jun;240:155–62. Available from: http://dx.doi.org/10.1016/j.neuroscience.2013.02.050
• 55. Roberts LD, Ashmore T, McNally BD, Murfitt SA, Fernandez BO, Feelisch M, et al. Inorganic nitrate mimics exercise-stimulated muscular fiber-Type switching and myokine and g-Aminobutyric acid release. Diabetes. 2017;66(3):674–88.
• 56. Farzad B, Rajabi H, Gharakhanlou R, Allison DJ, Hayat P, Jameie SB. Swimming training attenuates allodynia and hyperalgesia induced by peripheral nerve injury in an adult male rat neuropathic model: Effects on irisin and GAD65. Pain Med (United States) [Internet]. 2018 Nov 1 [cited 2021 May 10];19(11):2236–45. Available from: https://academic.oup.com/painmedicine/article/19/11/2236/4791839
• 57. Maddock RJ, Casazza GA, Fernandez DH, Maddock MI. Acute modulation of cortical glutamate and GABA content by physical activity. J Neurosci [Internet]. 2016 Feb 24 [cited 2021 May 10];36(8):2449–57. Available from: /pmc/articles/PMC6705493/
• 58. Coxon JP, Cash RFH, Hendrikse JJ, Rogasch NC, Stavrinos E, Suo C, et al. GABA concentration in sensorimotor cortex following high-intensity exercise and relationship to lactate levels. J Physiol [Internet]. 2018 Feb 15 [cited 2021 May 10];596(4):691–702. Available from: /pmc/articles/PMC5813602/
• 59. Barzroodi pour M, Bayat M, Golab F, Eftekharzadeh M, Katebi M, Soleimani M, et al. The effect of exercise on GABA signaling pathway in the model of chemically induced seizures. Life Sci [Internet]. 2019;232:116667. Available from: https://doi.org/10.1016/j.lfs.2019.116667
• 60. Huang SH, Yang SM, Lo JJ, Wu SH, Tai MH. Irisin gene delivery ameliorates burn-induced sensory and motor neuropathy. Int J Mol Sci [Internet]. 2020 Oct 2 [cited 2021 May 10];21(20):1–17. Available from: www.mdpi.com/journal/ijms
• 61. Akdogan I, Goksin N. Experimental Epilepsy Models and Morphologic Alterations of Experimental Epilepsy Models in Brain and Hippocampus. In: Underlying Mechanisms of Epilepsy [Internet]. InTech; 2011. Available from: http://www.intechopen.com/books/underlying-mechanisms-of-epilepsy/experimental-epilepsy-models-and-morphologic-alterations-of-experimental-epilepsy-models-in-brain-an
• 62. Erfanparast A, Tamaddonfard E. Effects of intracortical microinjection of vitamin B12 on penicillin-induced epileptiform activity in rats. Acta Neurobiol Exp (Wars). 2015;75(2):200–7.
• 63. Nierenberg AA, Ghaznavi SA, Sande Mathias I, Ellard KK, Janos JA, Sylvia LG. Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha as a Novel Target for Bipolar Disorder and Other Neuropsychiatric Disorders. Biol Psychiatry [Internet]. 2018;83(9):761–9. Available from: https://doi.org/10.1016/j.biopsych.2017.12.014